title: A double-blind, randomized phase II study to evaluate the safety and efficacy of acetyl-L-carnitine in the prevention of sagopilone-induced peripheral neuropathy.
abstract: Peripheral neuropathy (PN) is a recognized side effect of microtubule-targeting agents and the most clinically relevant toxicity observed with the epothilone sagopilone (SAG). Studies suggest that acetyl-L-carnitine (ALC) may prevent chemotherapy-induced PN. We conducted a prospective, placebo (PBO)-controlled, double-blind, randomized trial to investigate the safety and efficacy of ALC for the prevention of SAG-induced PN. Methods. Patients with ovarian cancer (OC) or castration-resistant prostate cancer (CRPC) and no evidence of neuropathy received SAG (16 mg/m(2) intravenously over 3 hours every 3 weeks) with ALC (1,000 mg every 3 days) or placebo (PBO). The primary endpoint was incidence of PN within six or fewer cycles in both treatment groups. Results. Overall, 150 patients enrolled (98 OC patients, 52 CRPC patients), with 75 per treatment arm. No significant difference in overall PN incidence was observed between treatment arms. The incidence of grade ≥3 PN was significantly lower in the ALC arm in OC patients. Median duration of neuropathy was similar between treatment arms. The best overall response (according to the modified Response Evaluation Criteria in Solid Tumors), response according to tumor markers, time-to-event variables, and discontinuations because of adverse events (AEs) were comparable between treatment arms. Conclusion. Administration of ALC with SAG did not result in a significant difference in overall PN incidence compared with a PBO. OC patients in the SAG/ALC arm had a significantly lower incidence of grade 3 or 4 PN compared with OC patients in the SAG/PBO arm.
authors.affiliation: Institut de Cancérologie de l'Ouest - René Gauducheau Centre de Recherche en Cancérologie, Nantes, France;
authors.forename: Mario
authors.initials: M
authors.lastname: Campone
authors.forename: Dominique
authors.initials: D
authors.lastname: Berton-Rigaud
authors.forename: Florence
authors.initials: F
authors.lastname: Joly-Lobbedez
authors.forename: Jean-Francois
authors.initials: JF
authors.lastname: Baurain
authors.forename: Frédéric
authors.initials: F
authors.lastname: Rolland
authors.forename: Arnulf
authors.initials: A
authors.lastname: Stenzl
authors.forename: Michel
authors.initials: M
authors.lastname: Fabbro
authors.forename: Marjan
authors.initials: M
authors.lastname: van Dijk
authors.forename: Jörg
authors.initials: J
authors.lastname: Pinkert
authors.forename: Thomas
authors.initials: T
authors.lastname: Schmelter
authors.forename: Natasja
authors.initials: N
authors.lastname: de Bont
authors.forename: Patricia
authors.initials: P
authors.lastname: Pautier
mesh_terms: D000108:Acetylcarnitine / Q000009:adverse effects / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D052160:Benzothiazoles / Q000009:adverse effects* / Q000627:therapeutic use; D004311:Double-Blind Method; D034261:Epothilones / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000517:prevention & control*; D011446:Prospective Studies; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy
chemical_list: D000970:Antineoplastic Agents; D052160:Benzothiazoles; D034261:Epothilones; D000108:Acetylcarnitine; C530494:sagopilone